Association of a genetic polymorphism of IL1RN with risk of acute pancreatitis in a Korean ethnic group
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background/Aims: Several epidemiological studies have validated the association of interleukin gene polymorphisms with acute pancreatitis (AP) in different populations. However, there have been few studies in Asian ethnic groups. We aimed to investigate the relationships between inflammatory cytokine polymorphisms and AP as pilot research in a Korean ethnic group. Methods: Patients who had been diagnosed with AP were prospectively enrolled. DNA was extracted from whole blood, and DNA sequencing was subsequently performed. Single-nucleotide polymorphisms (SNPs) of the interleukin 1β (IL1B), interleukin 1 receptor antagonist (IL1RN), and tumor necrosis factor α (TNFA) genes of patients with AP were compared to those of normal controls. Results: Between January 2011 and January 2013, a total of 65 subjects were enrolled (40 patients with AP vs. 25 healthy controls). One intronic SNP (IL1RN −1129T>C, rs4251961) was significantly associated with the risk of AP (odds ratio, 0.304; 95% confidence interval, 0.095 to 0.967; p = 0.043). However, in our study, AP was not found to be associated with polymorphisms in the promoter regions of inflammatory cytokine genes, including IL1B (−118C>T, c47+242C>T, +3954C/T, and −598T>C) and TNFA (−1211T>C, −1043C>A, −1037C>T, −488G>A, and −418G>A). Conclusions: IL1RN −1129T>C (rs4251961) genotypes might be associated with a significant increase of AP risk in a Korean ethnic group.
Abstract
Background/Aims: Several epidemiological studies have validated the association of interleukin gene polymorphisms with acute pancreatitis (AP) in different populations. However, there have been few studies in Asian ethnic groups. We aimed to investigate the relationships between inflammatory cytokine polymorphisms and AP as pilot research in a Korean ethnic group. Methods: Patients who had been diagnosed with AP were prospectively enrolled. DNA was extracted from whole blood, and DNA sequencing was subsequently performed. Single-nucleotide polymorphisms (SNPs) of the interleukin 1β (IL1B), interleukin 1 receptor antagonist (IL1RN), and tumor necrosis factor α (TNFA) genes of patients with AP were compared to those of normal controls. Results: Between January 2011 and January 2013, a total of 65 subjects were enrolled (40 patients with AP vs. 25 healthy controls). One intronic SNP (IL1RN −1129T>C, rs4251961) was significantly associated with the risk of AP (odds ratio, 0.304; 95% confidence interval, 0.095 to 0.967; p = 0.043). However, in our study, AP was not found to be associated with polymorphisms in the promoter regions of inflammatory cytokine genes, including IL1B (−118C>T, c47+242C>T, +3954C/T, and −598T>C) and TNFA (−1211T>C, −1043C>A, −1037C>T, −488G>A, and −418G>A). Conclusions: IL1RN −1129T>C (rs4251961) genotypes might be associated with a significant increase of AP risk in a Korean ethnic group.
참고문헌 (30)
- Lankisch PG, "Acute pancreatitis", Lancet, 386, pp.85~96 (2015)
- Johnson CD, "Acute pancreatitis", BMJ, 349, pp.g4859~ (2014)
- Tukiainen E, "Polymorphisms of the TNF, CD14, and HSPA1B genes in patients with acute alcohol-induced pancreatitis", Pancreas, 37, pp.56~61 (2008)
- Yin YW, "Influence of interleukin gene polymorphisms on development of acute pancreatitis: a systematic review and meta-analysis", Mol Biol Rep, 40, pp.5931~5941 (2013)
- Lee KJ, "Comparison of predictive systems in severe acute pancreatitis according to the revised Atlanta Classification", Pancreas, 45, pp.46~50 (2016)
- Cho JH, "Usefulness of scheduled follow-up CT in discharged patients with acute pancreatitis", Pancreatology, 15, pp.642~646 (2015)
- Cho JH, "EUS finding of geographic hyperechoic area is an early predictor for severe acute pancreatitis", Pancreatology, 12, pp.495~501 (2012)
- de-Madaria E, "Cytokine genotypes in acute pancreatitis: association with etiology, severity, and cytokine levels in blood", Pancreas, 37, pp.295~301 (2008)
- Mayer J, "Inflammatory mediators in human acute pancreatitis: clinical and pathophysiological implications", Gut, 47, pp.546~552 (2000)
- Norman J., "The role of cytokines in the pathogenesis of acute pancreatitis", Am J Surg, 175, pp.76~83 (1998)
- Banks PA, "Epidemiology, natural history, and predictors of disease outcome in acute and chronic pancreatitis", Gastrointest Endosc, 56(6 Suppl), pp.S226~S230 (2002)
- Bishehsari F, "TNF-alpha gene (TNFA) variants increase risk for multi-organ dysfunction syndrome (MODS) in acute pancreatitis", Pancreatology, 12, pp.113~118 (2012)
- Smithies AM, "Investigation of the interleukin 1 gene cluster and its association with acute pancreatitis", Pancreas, 20, pp.234~240 (2000)
- Stuber F, "A genomic polymorphism within the tumor necrosis factor locus influences plasma tumor necrosis factor-alpha concentrations and outcome of patients with severe sepsis", Crit Care Med, 24, pp.381~384 (1996)
- Santtila S, "Presence of the IL-1RA allele 2 (IL1RN*2) is associated with enhanced IL-1beta production in vitro", Scand J Immunol, 47, pp.195~198 (1998)
- Hu Z, "Allele 2 of the interleukin-1receptor antagonist gene (IL1RN*2) is associated with a decreased risk of primary lung cancer", Cancer Lett, 236, pp.269~275 (2006)
- Xue H, "Interleukin-1B and interleukin-1 RN polymorphisms and gastric carcinoma risk: a meta-analysis", J Gastroenterol Hepatol, 25, pp.1604~1617 (2010)
- Jae Hee Cho, "The IL-1B Genetic Polymorphism Is Associated with Aspirin-Induced Peptic Ulcers in a Korean Ethnic Group", Gut and Liver, 10(3), pp.362~368 (2016), 거트앤리버 소화기연관학회협의회
- El-Omar EM, "Interleukin-1 polymorphisms associated with increased risk of gastric cancer", Nature, 404, pp.398~402 (2000)
- Carrol ED, "The IL1RN promoter rs4251961 correlates with IL-1 receptor antagonist concentrations in human infection and is differentially regulated by GATA-1", J Immunol, 186, pp.2329~2335 (2011)
- Tarlow JK, "Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat", Hum Genet, 91, pp.403~404 (1993)
- Mansfield JC, "Novel genetic association between ulcerative colitis and the anti-inflammatory cytokine interleukin-1 receptor antagonist", Gastroenterology, 106, pp.637~642 (1994)
- Tarlow JK, "Severity of alopecia areata is associated with a polymorphism in the interleukin-1 receptor antagonist gene", J Invest Dermatol, 103, pp.387~390 (1994)
- Blakemore AI, "Interleukin-1receptor antagonist allele (IL1RN*2) associated with nephropathy in diabetes mellitus", Hum Genet, 97, pp.369~374 (1996)
- Reiner AP, "Polymorphisms of the IL1-receptor antagonist gene (IL1RN) are associated with multiple markers of systemic inflammation", Arterioscler Thromb Vasc Biol, 28, pp.1407~1412 (2008)
- Formela LJ, "Inflammatory mediators in acute pancreatitis", Br J Surg, 82, pp.6~13 (1995)
- Yin YW, "Association between tumor necrosis factor-alpha gene -308A", G polymorphism and the risk of acute pancreatitis: a meta-analysis, 2012, pp.178, 409~414
- Powell JJ, "Evidence against a role for polymorphisms at tumor necrosis factor, interleukin-1 and interleukin-1 receptor antagonist gene loci in the regulation of disease severity in acute pancreatitis", Surgery, 129, pp.633~640 (2001)
- Schneider A, "Hereditary, familial, and idiopathic chronic pancreatitis are not associated with polymorphisms in the tumor necrosis factor alpha (TNF-alpha) promoter region or the TNF receptor 1(TNFR1) gene", Genet Med, 5, pp.120~125 (2003)
- Zhang DL, "Association of polymorphisms of IL and CD14 genes with acute severe pancreatitis and septic shock", World J Gastroenterol, 11, pp.4409~4413 (2005)
